Rituximab Plus Corticosteroids in Non-infectious Active Mixed Cryoglobulinemia Vasculitis

Inclusion Criteria: 1. The patient must be at least 18 years of age or older, without any upper age limit 2. Patient informed and agreed to participate, and gave informed consent, 3. Patient with active cryoglobulinemia vasculitis define by positive cryoglobulinemia and a clinically active vasculitis with skin, joint, renal, peripheral nerve, central neurological, digestive, pulmonary and/or cardiac involvement (no histological evidence needed if presence of purpura demonstrated), 4. Patient with primary Sjögren's syndrome, systemic lupus erythematosus, or another auto-immune disease, or B-cell non-Hodgkin lymphoma (with cryoglobulinemia as the only therapeutic indication), or essential mixed cryoglobulinemia, 5. Naive or relapsing patients, without modification (initiation or increase) of immunosuppressive therapy in the month prior the inclusion, 6. For women of child bearing age: negative pregnancy test during the inclusion, and effective contraception during the period of 12 months after the latest rituximab infusion or placebo, 7. Patients with severe vasculitis must be treated in the 15 days prior inclusion by 3 bolus of methylprednisolone (15 mg/kg/d) AND 3 to 7 plasma exchanges (exchange volume of 60 ml/kg/session). Exclusion Criteria: 1. Patient with a medium and small size vessels vasculitis unrelated to cryoglobulinemia (granulomatous with polyangiitis (Wegener's disease), microscopic polyangiitis, eosinophilic granulomatous with polyangiitis (Churg-Strauss syndrome), polyarteritis nodose, IgA vasculitis, hypersensitivity vasculitis, infectious vasculitis, hypocomplementemic urticarial vasculitis), 2. Patient with a large size vessels vasculitis, 3. Patient with non active cryoglobulinemia vasculitis, 4. Patient with immunosuppressive therapy introduced or increased in the month prior to the inclusion, 5. Patients receiving corticosteroid therapy \> 0.5 mg/kg/d for more than one month before the inclusion or \> 1 mg/kg/d for more than two weeks before the inclusion, 6. Patient who had received rituximab therapy within the 12 months before the inclusion, 7. Pregnancy in progress or needed , breast feeding, 8. HIV-positive status, 9. Patient with active hepatitis B or C infection, 10. HBs Ag-positive and/or HBV DNA detectable in the blood\*, 11. Patients with known hypersensitivity reaction to the active substance or any of the excipients, or to murine proteins, 12. Contraindication to rituximab, 13. Active infections at screening, 14. Patient in guardianship, 15. Patient already included in a biomedical research protocol, 16. No social security scheme (Beneficiaries or eligible), 17. History of cancer during the last 3 years before inclusion, including solid tumors, hematological malignancies (except lymphoproliferative disorder associated with the mixed cryoglobulinemia vasculitis), and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been treated or excized and cured)" * If the hepatitis B core antibody (anti-HBc) is positive, the benefit/risk will be evaluated by an hepatologist before inclusion, and patient, if enrolled, will be monitored until the end of the study.